This effects of lead on reactions intermediate in oxidative phosphorylation and reversal of these effects by magnesium and EDTA will be studied. Lead is known to inhibit site I phosphorylation specifically by uncoupling this site. A combination of lead and ADP blocks this site. Mechanisms by which these actions occur will be studied in isolated mitochondria, submitochondrial particles and in perfused kidneys using dual wavelength spectrophotometry. The effects of lead on brain function will also be studied in lead intoxicated suckling rats by assaying norepinephrine levels in different brain areas. Effects of magnesium on the course of lead intoxication in dogs will be tested to confirm our observation that intravenous magnesium sulfate causes mobilization and increased excretion of lead. Lead intoxication in dogs will be followed by assays of blood lead and delta amino levulinic dehydrase activity. Nutritional studies on 60 gm rats have shown that a combination of low calcium and low magnesium in the diet allows much more rapid rate of lead poisoning. This lead will be followed intensively.